Endocrinology, Vol 128, 1623-1629, Copyright © 1991 by Endocrine Society

ARTICLES

Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines

SG Ren and GD Braunstein
Department of Medicine Cedars-Sinai Medical Center-University of California School of Medicine, Los Angeles 90048.

Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells. This study was performed to examine whether insulin also regulates the production of hCG by this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96, and 53 mg/L, respectively. Time- course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media. Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the presence of insulin and [35S]methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable [35S]methionine-hCG secreted into the medium than the control cultures (P less than 0.05). During this time period, human placental lactogen release and total trichloroacetice acid-precipitable [35S]methionine protein were not increased. The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation. Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells. We conclude that insulin stimulates the synthesis and secretion of hCG from JEG-3 cells and JAR cells, and that hCG regulation in choriocarcinoma cells differs from that in primary human placental trophoblast cells. The effect of insulin on JEG-3 cells may be mediated in part through the insulin-like growth factor-I receptor.

This article has been cited by other articles:

				R. Coya, O. Gualillo, J. Pineda, M. del Carmen Garcia, M. d. l. A. Busturia, A. Aniel-Quiroga, P. Martul, and R. Maria Senaris Effect of Cyclic 3',5'-Adenosine Monophosphate, Glucocorticoids, and Insulin on Leptin Messenger RNA Levels and Leptin Secretion in Cultured Human Trophoblast Biol Reprod, September 1, 2001; 65(3): 814 - 819. [Abstract] [Full Text] [PDF]

				R. Yu, S.-G. Ren, G. A. Horwitz, Z. Wang, and S. Melmed Pituitary Tumor Transforming Gene (PTTG) Regulates Placental JEG-3 Cell Division and Survival: Evidence from Live Cell Imaging Mol. Endocrinol., August 1, 2000; 14(8): 1137 - 1146. [Abstract] [Full Text]

				A. Koman, S. Cazaubon, P.-O. Couraud, A. Ullrich, and A. D. Strosberg Molecular Characterization and in Vitro Biological Activity of Placentin, a New Member of the Insulin Gene Family J. Biol. Chem., August 23, 1996; 271(34): 20238 - 20241. [Abstract] [Full Text] [PDF]